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Titolo:
Disruption of cell adhesion and caspase-mediated proteolysis of beta- and gamma-catenins and APC protein in paclitaxel-induced apoptosis
Autore:
Ling, YH; Zhong, Y; Perez-Soler, R;
Indirizzi:
NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA NYU New York NY USA 10016 lan Comprehens Canc Ctr, New York, NY 10016 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 3, volume: 59, anno: 2001,
pagine: 593 - 603
SICI:
0026-895X(200103)59:3<593:DOCAAC>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALPHA-CATENIN; EPITHELIAL-CELLS; ENDOTHELIAL-CELL; TUMOR-CELLS; N-CADHERIN; DEATH; CLEAVAGE; PLAKOGLOBIN; TAXOL; ASSOCIATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Ling, YH NYU, Sch Med, Kaplan Comprehens Canc Ctr, 550 1st Ave, New York, NY 10016 USA NYU 550 1st Ave New York NY USA 10016 Ave, New York, NY 10016 USA
Citazione:
Y.H. Ling et al., "Disruption of cell adhesion and caspase-mediated proteolysis of beta- and gamma-catenins and APC protein in paclitaxel-induced apoptosis", MOLEC PHARM, 59(3), 2001, pp. 593-603

Abstract

Cell adhesion is important in the regulation of cell proliferation, migration, survival, and apoptosis. The major components of cell adhesion are thecadherin family of proteins, alpha-, beta- and gamma -catenins, and cytoskeletons. In addition, beta -catenin, when associated with adenomatous polyposis coli (APC) protein, an oncosuppressor, is implicated in the regulationof beta -catenin/APC-related signaling pathways. To examine the correlation between impairment of cell adhesion events and apoptosis, we used human non-small-cell lung cancer H460 and H520 cell lines as models to determine whether paclitaxel-induced apoptosis is associated with disruption of the components of cell adhesion and their functions. Paclitaxel treatment resulted in cells rounding up and losing contact with their neighboring cells, suggesting that the drug does indeed affect cell adhesion and related events. Western blot analysis revealed that paclitaxel caused a time- and concentration-dependent cleavage of beta -catenin, gamma -catenin, and APC protein, but not alpha -catenin or E-cadherin. These cleavages of beta -catenin and gamma -catenin were apoptosis-dependent, not mitosis-dependent. Paclitaxel treatment led to the proteolysis and activation of caspase-3 and -7, but not caspase-1. Furthermore, paclitaxel-induced apoptosis and cleavage of beta- catenin and gamma -catenin were inhibited by the pan-caspase inhibitor Z-VAD-FMK and partially inhibited by the caspase-3 inhibitor Z-DEVD-FMK but were not affected by the caspase-1 inhibitor AC-YVAD-CMK. Although the pan-caspase inhibitor blocked the cleavage of beta -catenin as well as DNA fragmentation, it did not affect paclitaxel-induced M-phase arrest and only partially prevented cell-growth inhibition. Biochemical studies revealed that cleaved beta -catenin was detected only in the Triton X-100 insoluble fraction, suggesting that it might localize in nuclear and/or membrane structures. Interestingly, the paclitaxel-induced beta -catenin fragment lost its ability to bind to E-cadherin, alpha -catenin, or APC protein and to serve as a substrate for tyrosine kinase. All our data demonstrate that the caspase-mediated cleavage of beta -catenin, gamma -catenin, and APC protein might contribute to paclitaxel-induced apoptosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:21:33